Damage In Brain Regions Research Articles

The emerging role of norepinephrine in cognitive dysfunctions of Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 1% of the population over age 60. In those patients cognitive dysfunction is a persistent issue that impairs quality of life and productivity. Neuropathological studies demonstrate significant damage in brain regions outside the nigral dopamine (DA) system, including early degeneration of locus coeruleus norepinephrine (LC-NE) neurons, yet discussion of PD and treatment focus has remained dopaminergic-based. Motor symptoms benefit from DA replacement for many years, but other symptoms including several cognitive deficits continue unabated. Recent interest in non-DA substrates of PD highlights early involvement of LC-NE neurons and provides evidence for a prodromal phase, with cognitive disturbance, even in sporadic PD. We outline insights from basic research in LC-NE function to clinical and pathological evidence highlighting a role for NE in PD cognitive dysfunction. We propose that loss of LC-NE regulation, particularly in higher cortical regions, critically underlies certain cognitive dysfunctions in early PD. As a major unmet need for patients, research and use of NE drugs in PD may provide significant benefits for cognitive processing.

Longitudinal Magnetization Transfer Imaging in Mild to Severe Alzheimer Disease

MTI has been proposed as a sensitive technique for studying microstructural brain tissue changes in patients with AD, but the course of these changes over time is largely unknown. We therefore used a placebo-controlled study of memantine to follow the evolution of tissue damage in AD by means of MTR measurements and investigated how MTR changes were related to brain atrophy and cognition. Twenty-eight patients (76.5 ± 5.8 years) with mild to moderate AD underwent MTI, brain volume measurements, and cognitive testing at baseline and after 6 and 12 months. Nineteen healthy individuals (73.3 ± 3.2 years) served as controls. MTI was performed with a 2-minute protocol that was optimized for an enhanced MT effect and reduced motion sensitivity. Global and regional MTR measurements served as correlations with brain volumes and the MMSE score. AD patients had significantly lower global MTR values than controls, and showed a consistent and significant MTR reduction in all regions investigated over a period of 12 months. These MTR changes were paralleled by a brain tissue loss of 2.2% per year. Associations between MTR and cognition were found for the hippocampus, putamen, and thalamus, and were more pronounced in the left hemisphere. MTI in AD allows the assessment of ongoing global and regional brain damage independent of atrophy, and therefore appears to be a valuable marker for disease-related tissue changes.

Regional Cerebral Blood Flow Abnormalities in Patients With Kawasaki Disease

Kawasaki disease (KD) is an acute febrile disorder of unknown etiology. Brain single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) help in detecting regional cerebral blood flow abnormalities and brain damage. The usefulness of SPECT and MRI in patients with KD was evaluated. All 22 patients with KD underwent brain SPECT using Tc-99m-hexamethyl propylene amine oxime from 6 days to 3 years after onset, and 8 patients underwent brain MRI. Of the 22 patients, 4 had neurologic symptoms. Case 1 showed prolonged apnea; case 2, prolonged disturbance of consciousness; and cases 3 and 4 generalized tonic-clonic seizures. Initial brain SPECT showed localized hypoperfusion in 4 and 13 patients with and without neurologic symptoms, respectively. All patients with neurologic symptoms underwent follow-up SPECT; localized hypoperfusion was detected between 1- and 6-month follow-up in 3 of these patients. Six patients without neurologic symptoms underwent follow-up SPECT. Localized hypoperfusion was detected at approximately 1- to 11-month follow-up in 4 of these patients. Diffusion-weighted imaging revealed abnormal high-intensity areas in the corpus callosum in case 1. Case 2 showed a bilateral chronic subdural hematoma with decreased size and ischemic changes, and case 3 showed bilateral hippocampal atrophy and left hippocampal sclerosis. Because the occurrence of localized hypoperfusion is possibly not restricted to only the acute phase in KD, brain SPECT and MRI should also be performed in KD patients with neurologic symptoms.

Biological outcome measurements for behavioral interventions in multiple sclerosis

Behavioral interventions including exercise, stress management, patient education, psychotherapy and multidisciplinary neurorehabilitation in general are receiving increasing recognition in multiple sclerosis (MS) clinical practice and research. Most scientific evaluations of these approaches have focused on psychosocial outcome measures such as quality of life, fatigue or depression. However, it is becoming increasingly clear that neuropsychiatric symptoms of MS are at least partially mediated by biological processes such as inflammation, neuroendocrine dysfunction or regional brain damage. Thus, successful treatment of these symptoms with behavioral approaches could potentially also affect the underlying biology. Rigidly designed scientific studies are needed to explore the potential of such interventions to affect MS pathology and biological pathways linked to psychological and neuropsychiatric symptoms of MS. Such studies need to carefully select outcome measures on the behavioral level that are likely to be influenced by the specific intervention strategy and should include biomarkers with evidence for an association with the outcome parameter in question. In this overview, we illustrate how biological and psychological outcome parameters can be combined to evaluate behavioral interventions. We focus on two areas of interest as potential targets for behavioral interventions: depression and fatigue.

Biochemical Markers in Perinatal Asphyxia

Early assessment of the severity of an acute cerebral lesion secondary to hypoxia-ischemia or other pathologic conditions may provide a very useful basis for preventive or therapeutic decisions in pediatric patients. In the present review, we discuss the diagnostic and prognostic value of a series of biochemical parameters, with special reference to the diagnosis of neonatal HIE. Currently many specific biochemical markers of brain injury are being investigated to assess regional brain damage after perinatal asphyxia in neonates of which serum protein S-100β, brain-specific creatine kinase, neuron-specific enolase, IL6 and urinary uric acid levels appear promising in identifying patients with a risk of developing hypoxic-ischemic encephalopathy. Whether detection of elevated serum concentrations of these proteins reflects long-term neurodevelopmental impairment remains to be investigated. Key words: S-100; Brain specific creatine kinase; neuron specific enolase; IL6; urinary uric acid; hypoxic ischaemic cerebral injury. DOI: 10.3126/jnps.v31i2.4155 J Nep Paedtr Soc 2010;31(2):151-156

Clinical relevance of brain volume changes in patients with cerebrotendinous xanthomatosis

ObjectiveTo quantify total and regional brain damage in subjects with cerebrotendinous xanthomatosis (CTX) using MR based quantitative measures.BackgroundCTX is a rare inherited disorder characterised by progressive neurological impairment. Appropriate therapy...

Fluoxetine Might Alleviate Brain Damage and Hypercortisolemia Related to Chronic Alcohol in Rats

The aims of this study were (a) to investigate the neuropathological damage in brain regions and changes of corticosteroid concentrations related to chronic alcohol administration, (b) to see what effect fluoxetine (Prozac) has on the neuropathological damage and corticosteroid levels, and (c) to evaluate the potential association between neuropathological damage and changes of corticosteroid levels. Rats were randomly divided into alcohol and control groups, with the former given ethanol intraperitoneally for 8 weeks; corticosterone levels were measured in both groups. Thereafter, fluoxetine hydrochloride or saline was injected into the animals. The rats were sacrificed and the number of neurons in five regions of the cerebral cortex was determined. The numbers of neurons in the frontal cortex, parietal cortex, and CA3 regions of the hippocampus of the alcoholic group treated with saline were significantly reduced compared with the control group treated with saline. The number of neurons observed in CA3 regions of the hippocampal cortex of the alcoholic group treated with fluoxetine was significantly increased compared with the alcoholic group treated with saline. Corticosteroid levels of the alcoholic group treated with saline were significantly increased compared with the control group. Corticosteroid levels of the alcoholic group treated with fluoxetine were obviously reduced compared with the alcoholic group treated with saline. The number of neurons in the CA3 regions of the hippocampus was adversely associated with corticosteroid levels. Chronic alcohol administration induced selective loss of neurons in different brain regions and increased corticosteroid concentrations. Fluoxetine may have alleviated neuronal loss in the hippocampus and attenuated hypercortisolemia related to alcohol.

Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats

Polychlorinated biphenyls (PCBs) are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Free radicals represent a class of biologically generated species that pose a potential threat to neuronal survival. Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase-4 (GPx-4) are the key cellular antioxidant enzymes by which neurons and other cells detoxify free radicals and protect themselves from damage. Melatonin, an indoleamine plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector. The aim was to carry out to investigate the effect of melatonin on PCB (Aroclor 1254) induced changes in histomorphology and Cu/Zn SOD, GPx-4 mRNA expression in selected brain regions of adult rats. Group I: rats intraperitoneally (i.p.) administered with corn oil (vehicle) for 30 days. Group II: rats injected (i.p.) with Aroclor 1254 (PCB) at 2 mg/kg bw/day for 30 days. Groups III and IV: rats (i.p.) received melatonin (5 or 10 mg/kg bw/day) simultaneously with PCB for 30 days. Groups V and VI: rats (i.p.) received melatonin (5 or 10 mg/kg bw/day) alone for 30 days. After 30 days, rats were sacrificed and the brain regions were dissected to cerebral cortex, cerebellum and hippocampus. Activities of enzymatic antioxidants such as total SOD, Cu/Zn SOD, Mn SOD, glutathione peroxidase (GPx) were estimated. mRNA expressions of Cu/Zn SOD and GPx-4 were quantified by reverse transcriptase polymerase chain reaction (RT-PCR) method. Histological study was also observed. Specific activities of all antioxidant enzymes and mRNA expression of Cu/Zn SOD and GPx-4 were decreased in brain regions of PCB exposed animals. Neuronal damages were observed in all the brain regions. Exogenous melatonin supplementation retrieved all the parameters. These results suggest that melatonin protects PCB-induced oxidative stress and prevents neuronal damage in brain regions.

Loss of astrocytic glutamate transporters in Wernicke encephalopathy.

Wernicke encephalopathy (WE), a neurological disorder caused by thiamine deficiency (TD), is characterized by structural damage in brain regions that include the thalamus and cerebral cortex. The basis for these lesions is unclear, but may involve a disturbance of glutamatergic neurotransmission. We have therefore investigated levels of the astrocytic glutamate transporters EAAT1 and EAAT2 in order to evaluate their role in the pathophysiology of this disorder. Histological assessment of the frontal cortex revealed a significant loss of neurons in neuropathologically confirmed cases of WE compared with age-matched controls, concomitant with decreases in alpha-internexin and synaptophysin protein content of 67 and 52% by immunoblotting. EAAT2 levels were diminished by 71% in WE, with levels of EAAT1 also reduced by 62%. Loss of both transporter sites was confirmed by immunohistochemical methods. Development of TD in rats caused a profound loss of EAAT1 and EAAT2 in the thalamus accompanied by decreases in other astrocyte-specific proteins. Treatment of TD rats with N-acetylcysteine prevented the downregulation of EAAT2 in the medial thalamus, and ameliorated the loss of several other astrocyte proteins, concomitant with increased neuronal survival. Our results suggest that (1) loss of EAAT1 and EAAT2 glutamate transporters is associated with structural damage to the frontal cortex in patients with WE, (2) oxidative stress plays an important role in this process, and (3) TD has a profound effect on the functional integrity of astrocytes. Based on these findings, we recommend that early treatment using a combination of thiamine AND antioxidant approaches should be an important consideration in cases of WE.

Perinatal Asphyxia in Preterm Neonates Leads to Serum Changes in Protein S-100 and Neuron Specific Enolase

In preterm infants, neurological signs and clinical manifestations of brain damage are limited criteria for diagnosis of neurologic sequelae. Early indicators of brain damage are needed and currently some specific biochemical markers of brain injury are investigated to assess regional brain damage after perinatal asphyxia in neonates. In this study Protein S-100 (PS-100) and Neuron Specific Enolase (NSE) serum levels were studied serially during the perinatal period in preterm neonates with perinatal asphyxia as markers of glial and neuronal damage respectively. Thirty outborn preterm infants with perinatal asphyxia were studied at 3, 24, 48 hours and 7 days of life. According to Apgar scores at 1' and cord blood pH and lacticidemia (LA), patients were divided in two groups: 15 of them (GA 33+/-1.2 wk, BW 1790+/-383 g) with severe asphyxia (Apgar <4, pH7.0+/-0.08, LA 6.29+/-0.79 mM/L) and 15 (GA 32+/-1.8 wk, BW 1810+/-290 g) with mild asphyxia (Apgar between 4-6, pH 7.18+/-0.05, LA 2.59+/-0.61 mM/L). Ten gestational age matched healthy preterm neonates were studied as control group. Cerebral ultrasound examinations (7 MHz) were performed at birth and repeated at 3 weeks of life. The results of this study show that neonates with severe asphyxia at any time had significantly more elevated mean serum levels of both markers compared to the group with mild asphyxia and to the control group (p<0.05). The values of control group were also significantly lower in comparison with that of mild asphyxia. In neonates with severe asphyxia, NSE values decreased constantly from birth to the seventh day of life, while PS-100 showed a different pattern increasing progressively between 3 h and 7 days. In neonates with mild asphyxia serum values of both markers showed decreasing levels through the study period. The results of this study suggest that perinatal asphyxia is associated with the release of different brain cellular proteins in the blood of preterm infants with different time course indicating specific regional cellular injury. The more elevated levels of NSE at birth found in the newborns with severe asphyxia could be considered as an early biomarker of neuronal necrotic damage in the ischaemic phase of perinatal cerebral hypoxic-ischaemic insult; progressive increase of PS-100 during the first week of life in the same neonates could be expression of apoptotic damage of glial cells occurring in the reperfusion phase of cerebral ischaemia.

A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis

The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR-based approach. Using a 3 Tesla scanner, dual-echo, 3D fast-field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel-based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical-subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto-occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2-visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology.

The Neuropathology of Alcohol-Related Brain Damage

Excessive alcohol use can cause structural and functional abnormalities of the brain and this has significant health, social and economic implications for most countries in the world. Even heavy social drinkers who have no specific neurological or hepatic problems show signs of regional brain damage and cognitive dysfunction. Changes are more severe and other brain regions are damaged in patients who have additional vitamin B1 (thiamine) deficiency (Wernicke-Korsakoff syndrome). Quantitative studies and improvements in neuroimaging have contributed significantly to the documentation of these changes but mechanisms underlying the damage are not understood. A human brain bank targeting alcohol cases has been established in Sydney, Australia, and tissues can be used for structural and molecular studies and to test hypotheses developed from animal models and in vivo studies. The recognition of potentially reversible changes and preventative medical approaches are important public health issues.

Developmental phonagnosia: A selective deficit of vocal identity recognition

Phonagnosia, the inability to recognize familiar voices, has been studied in brain-damaged patients but no cases due to developmental problems have been reported. Here we describe the case of KH, a 60-year-old active professional woman who reports that she has always experienced severe voice recognition difficulties. Her hearing abilities are normal, and an MRI scan showed no evidence of brain damage in regions associated with voice or auditory perception. To better understand her condition and to assess models of voice and high-level auditory processing, we tested KH on behavioural tasks measuring voice recognition, recognition of vocal emotions, face recognition, speech perception, and processing of environmental sounds and music. KH was impaired on tasks requiring the recognition of famous voices and the learning and recognition of new voices. In contrast, she performed well on nearly all other tasks. Her case is the first report of developmental phonagnosia, and the results suggest that the recognition of a speaker's vocal identity depends on separable mechanisms from those used to recognize other information from the voice or non-vocal auditory stimuli.

Neurobehavioral sequelae of traumatic brain injury: evaluation and management

Traumatic brain injury (TBI) is a worldwide public health problem. Over the last several decades, improvements in acute care have resulted in higher survival rates. Unfortunately, the majority of survivors of moderate and severe TBI have chronic neurobehavioral sequelae, including cognitive deficits, changes in personality and increased rates of psychiatric illness. These neurobehavioral problems are understandable in the context of the typical profile of regional brain damage associated with trauma. This paper presents an overview of the neurobehavioral sequelae of TBI and outlines issues to consider in the evaluation and management of these challenges.

Chronic Hypertension Aggravates Heat Stress–Induced Cognitive Dysfunction and Brain Pathology

Hyperthermia following heat stress results in profound brain edema formation and damage to the central nervous system (CNS). However, whether acute or chronic diseases such as cardiovascular, endocrine, or metabolic ailments further influence the vulnerability of human populations to heat-related deaths is still unclear. In this investigation, we examined the effect of hyperthermia on chronic hypertensive rats. The influence of growth hormone (GH) as a therapy to attenuate brain dysfunction was also evaluated. Subjecting rats to 4 h of heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator resulted in profound impairment of motor and cognitive functions, breakdown of the blood-brain barrier (BBB), reduction in regional cerebral blood flow (CBF), edema formation, and brain damage. These effects were further aggravated when chronic hypertensive rats (two-kidney, one-clip model for 4 weeks) were subjected to similar hyperthermic conditions (38 degrees C for 4 h). Interestingly, the behavioral alterations and impairment of motor and cognitive functions in hypertensive rats were much worse than those in the normotensive animals subjected to heat stress. Pretreatment with GH (50 microg/kg/min i.v. for 60 min, before heat stress) significantly attenuated behavioral and cognitive deficits in normotensive rats and reduced the BBB dysfunction and brain pathology. On the other hand, similar treatment with GH in hypertensive animals only mildly reduced brain damage or cognitive dysfunction after heat stress. These novel observations indicate that patients suffering from various chronic diseases respond differently to various health hazards such as hyperthermia and to other neuroprotective agents.

Research on the relationship between brain anoxia at different regional oxygen saturations and brain damage using near-infrared spectroscopy

The objective of this paper is to investigate the difference in physiological parameters, EEG and morphology of brain tissues in newborn pigs with different regional oxygen saturations of brain (rSO2) and provide a basis for the determination of brain injury and degree of injury with the rSO2 in clinical practice. A noninvasive near-infrared spectroscopy (NIRS) technique was used to monitor the rSO2 of 27 newborn pigs. After mechanical ventilation and inhalation of 3–11% oxygen for 30 min by the newborn pigs, the pigs were grouped according to the rSO2 in the brain caused by inhalation of different concentrations of oxygen. There were six animals each in rSO2 < 30%, 30–35%, 35–40%, 40–50% groups and three animals in the rSO2 > 60% group (normal control). The physiological parameters and the EEG were monitored during the experiment. The animals were sacrificed by decollation at 72 hours after brain injury, and light microscope examination and pathological analysis of the ultrastructure were conducted on the brain tissues in the CA1 zone of hippocampi. In rSO2 > 40% groups, the mean arterial pressure (MAP) was stable and there were no significant changes in blood lactic acid, amplitudes of the EEG, light microscopic findings and ultrastructure after hypoxia. When the rSO2 was between 30% and 40%, the MAP was stable, the level of blood lactic acid increased, metabolic acidosis occurred, there was no significant change in the amplitudes of the EEG, there were ischemic changes in brain tissues under a light microscope and there was an injury of mitochondria in the neurons in the CA1 zone of hippocampi. When the rSO2 was less than 30%, circulatory failure occurred, the level of blood lactic acid increased, there was serious metabolic acidosis, the amplitudes of the EEG significantly decreased, there were vacuolization and broken fragments of cells under the light microscope and the mitochondria in the neurons in the CA1 zone of hippocampi were seriously injured. Under varying degrees of hypoxia, when the rSO2 is between 30% and 40%, brain injury occurs and the functional zones of mitochondria are injured in newborn pigs. When the rSO2 is less than 30%, the brain functions are seriously abnormal, and the serious morphological impairment in the functional zones of mitochondria is the basis for the disturbance of energy metabolism in brain neurocytes after hypoxia and the sequelae of the nervous system.

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: Preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.

Interoceptive Basis to Craving

SummaryAwareness of one's physiology is an important component of emotion. How might these processes be related to addiction? In a recent issue of Science, Naqvi et al. demonstrated that smoking addiction is disrupted by damage to the insula cortex. This suggests that brain circuits mediating interoception also contribute to craving states.

Antioxidant Effects of SelegilIne in Oxidative Stress Induced by Iron Neonatal Treatment in Rats

Increased levels of iron in specific brain regions have been reported in neurodegenerative disorders. It has been postulated that iron exerts its deleterious effects on the nervous system by inducing oxidative damage. In a previous study, we have shown that iron administered during a particular period of the neonatal life induces oxidative damage in brain regions in adult rats. The aim of the present study was to evaluate the possible protective effect of selegiline, a monoamino-oxidase B (MAO-B) inhibitor used in pharmacotherapy of Parkinson's disease, against iron-induced oxidative stress in the brain. Results have shown that selegiline (1.0 and 10.0 mg/kg), when administered early in life was able to protect the substantia nigra as well as the hippocampus against iron-induced oxidative stress, without affecting striatum. When selegiline (10.0 mg/kg) was administered in the adult life to iron-treated rats, oxidative stress was reduced only in the substantia nigra.

The neurotoxicity of alcohol

Patterns of drinking are changing throughout the world and in many countries this will be detrimental to the health and welfare of the local population. Even uncomplicated alcoholics who have no specific neurological or hepatic problems show signs of regional brain damage and cognitive dysfunction. Many of these changes are exaggerated and other brain regions damaged in patients who have additional vitamin B1 (thiamine) deficiency (Wernicke-Korsakoff syndrome). Quantitative neuropathology techniques and improvements in neuroimaging have contributed significantly to the documentation of these changes but mechanisms underlying the damage are not understood. A human brain bank targeting alcohol cases has been established in Sydney, Australia and provides fresh and frozen tissue for alcohol researchers. The tissues can be used to test hypotheses developed from structural neuropathological studies or from animal models and in vitro studies. Identification of reversible pathological changes and preventative medical approaches in alcoholism should enhance rehabilitation and treatment efforts, thereby mitigating debilitating morbidities and reducing mortality associated with this universal public health problem.